ALLHAT: Setting the Record Straight

From The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Case Western Reserve University, Cleveland, Ohio; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Tulane University Health Sciences Center, New Orleans, Louisiana.

Curt D. Furberg, MD, PhD

From The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Case Western Reserve University, Cleveland, Ohio; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Tulane University Health Sciences Center, New Orleans, Louisiana.

Jackson T. Wright Jr., MD, PhD

From The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Case Western Reserve University, Cleveland, Ohio; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Tulane University Health Sciences Center, New Orleans, Louisiana.

Jeffrey A. Cutler, MD, MPH

From The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Case Western Reserve University, Cleveland, Ohio; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Tulane University Health Sciences Center, New Orleans, Louisiana.

Paul Whelton, MD, MSc

From The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Case Western Reserve University, Cleveland, Ohio; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Tulane University Health Sciences Center, New Orleans, Louisiana.

From The University of Texas Health Science Center at Houston School of Public Health, Houston, Texas; Wake Forest University School of Medicine, Winston-Salem, North Carolina; Case Western Reserve University, Cleveland, Ohio; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland; and Tulane University Health Sciences Center, New Orleans, Louisiana.

Grant Support: By the National Heart, Lung, and Blood Institute (contract N01-HC-35130). The ALLHAT investigators received study medications from Pfizer (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin) and financial support from Pfizer.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, multicenter clinical trial, was designed to determine whether the incidence of coronary heart disease (CHD) is reduced in high-risk patients with hypertension by a calcium-channel blocker (represented by amlodipine), an angiotensin-converting enzyme (ACE) inhibitor (represented by lisinopril), or an α-blocker (represented by doxazosin), each compared with diuretic treatment (represented by chlorthalidone) (1). The overall findings of the trial, summarized in Table 1, showed that CHD risk was not improved for any of the 3 newer agents compared with chlorthalidone (2, 3) and that total mortality was similar for the 4 groups. However, diuretic-based therapy was superior to α-blocker–based, ACE inhibitor–based, and calcium-channel blocker–based therapy in preventing 1 or more major forms of cardiovascular disease (CVD), including stroke and heart failure. Results were consistent for all outcomes by age, sex, diabetic status, and ethnicity, except for stroke and combined CVD. For these end points, we found significant heterogeneity in the lisinopril–chlorthalidone comparison by ethnicity: Black persons assigned to chlorthalidone had a greater reduction in risk for stroke and CVD, in keeping with larger blood pressure differences. On the basis of these findings, the ALLHAT investigators recommended that diuretics should be the drug of choice for initial hypertension therapy and, since most hypertensive patients require more than 1 drug, that diuretics should generally be part of any antihypertensive regimen.

Since the publication of the ALLHAT findings, there has been considerable reaction (favorable and unfavorable) from around...